Part of the Bochum research team: Klaus Gerwert (left) and Léon Beyer. Credit: RUB, Marquard
Alzheimer’s disease is the most common form of dementia, and can follow a progressive symptom-free course of up to 15-20 years, posing difficulties for early detection and management. Additionally, current diagnostic methods for detecting amyloid plaques may include expensive PET scans or invasive lumbar puncture methods. A study recently published by a team led by Ruhr-University Bochum researchers has now shown that a blood test utilizing an immuno-infrared sensor to detect amyloid-beta misfolding could determine the risk of Alzheimer’s disease up to 17 years before first clinical symptoms.
The study was conducted by analyzing blood plasma from participants in the ESTHER study, a community-based prospective longitudinal study of older adults in Germany, whose blood samples were collected and frozen between 2000 and 2002. The researchers analyzed samples from 68 participants with Alzheimer’s disease, who had not been diagnosed at the time of the blood draws, as well as 240 control subjects without an Alzheimer’s diagnosis. The immuno-infrared sensor used for measurement provides a relative measurement of the structural properties of proteins, and could therefore be used to monitor aggregation or misfolding of proteins such as amyloid-beta, the authors wrote. The team also utilized complementary single-molecule array (SIMOA) technology and assessed additional biomarkers, including phosphorylated tau 181 (P-tau181) and glial fibrillary acidic protein (GFAP).
The researchers found that the sensor was able to identify the 68 subjects who later developed Alzheimer’s disease with a high degree of test accuracy. Using the SIMOA technology, the team further determined that the P-tau181 biomarker was not suitable for early symptom-free phase Alzheimer’s disease detection, according to corresponding author Klaus Gerwert, but GFAB concentration could indicate the disease up to 17 years before the clinical phase, though less precisely than the immuno-infrared sensor. Using the amyloid-beta misfolding and GFAB data together, the researchers could further improve the accuracy of the test in the symptom-free stage. This study was published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
“Our goal is to determine the risk of developing Alzheimer’s dementia at a later stage with a simple blood test even before the toxic plaques can form in the brain, in order to ensure that a therapy can be initiated in time,” said Gerwert.
The researchers noted that many proposed Alzheimer’s drugs fail in clinical trials due to the irreversible damage caused by amyloid plaques once they form.
“The exact timing of therapeutic intervention will become even more important in the future. The success of future drug trials will depend on study participants being correctly characterised and not yet showing irreversible damage at study entry,” said first author Léon Beyer.
The team is hoping to eventually bring their sensing technology to market maturity through a newly-founded start-up called betaSENSE, and ultimately have it approved as a diagnostic device for use in clinical laboratories.